Cephalosporin antibiotics having a chloro group bonded directly to the 3-position carbon atom of the 3-cephem ring have been described by R. R. Chauvette in U.S. Pat. Nos. 3,925,372 and 3,962,227 and copending application Ser. No. 656,240 filed Feb. 9, 1976, now U.S. Pat. No. 4,064,343. The 3-chloro-3-cephem antibiotics are prepared by the chlorination of a 3-hydroxy-3-cephem ester intermediate, preferably with phosphorus trichloride in the presence of dimethylformamide. The described reaction is illustrated by the following reaction scheme: ##STR1## wherein R is a carboxylic acid protecting ester forming group.
The 3-chloro substituted cephalosporins are highly effective in the treatment and control of bacterial infections. In particular, 7-(D-phenylglycylamido)-3-chloro-3-cephem-4-carboxylic acid (U.S. Pat. No. 3,925,372) is highly effective when administered orally. Because of the importance of cephalosporin antibiotics in the treatment of infectious diseases, methods for their economical large scale production are highly desirable.
This invention is concerned with the preparation of 3-chloro substituted cephalosporin antibiotics. In particular, it is concerned with a process for converting 7.beta.-acylamido-3-hydroxy-3-cephem ester sulfoxides (1-oxides) to the corresponding 7.beta.-acylamido-3-chloro-3-cephem ester sulfides.